Physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells

We have previously shown that physiological concentrations of zinc (7×10^–6 M) inhibit the release of histamine from human basophil leukocytes (Maroneet al., J. Pharmacol. Exp. Ther. 217: 292, 1981). In these experiments we compared the effect of zinc chloride on the release of chemical mediators from human basophils and mast cells isolated from human lung. Preincubation (5 min, 37°C) of human basophils and lung mast cells with zinc chloride (10^–6–3×10^–5 M) caused dose-related inhibition of histamine and peptide leukotriene C₄ (LTC₄) release induced by anti-IgE. Increase Ca²⁺ concentrations (0.3 to 6 mM) in the extracellular medium completely reversed the inhibitory effect of zinc on anti-IgE-mediated histamine secretion. Zinc chloride was a competitive antagonist of the action of Ca²⁺ in histamine secretion induced by anti-IgE with a dissociation constant (Kd) of about 10^–5 M in both the basophil and mast cell systems. Thus physiological concentrations of zinc inhibit the release of histamine from human basophils and lung mast cells, presumably by blocking Ca²⁺ uptake induced by anti-IgE activation.     

Characterization of potassium channels in mast cell plasma membranes: Their possible existence and involvement in potassium-evoked histamine release

The effects of three K⁺-channel blockers, quinine, quinidine and sparteine on K⁺-evoked histamine (HA) release have been investigated. KCl (150 mM) initiated 40–55% release of HA from rat peritoneal mast cells in the absence of extracellular Ca⁺⁺, and this could be suppressed by pretreating the cells with K⁺-channel blockers. In the concentration range of 0.05–2 mM, reductions were dose-dependent and the IC₅₀-s (in mM) obtained were 0.15 and 0.25 for quinine and quinidine and 0.20 for sparteine. The light microscopic studies showed close parallelism between the KCl-evoked HA-release and mast cell degranulation in the absence and also in the presence of K⁺-channel blockers. Present results strenghthened the involvement of K⁺-channels in the KCl-evoked HA release and showed that these channels are sensitive to quinine/quinidine and also to sparteine. These data appeared, however, insufficient to clarify fully the mechanism of K⁺-induced HA secretion or to classify the K⁺-channels involved in this mechanism.

     

Characterization of potassium channels in mast cell plasma membranes: Their possible existence and involvement in potassium-evoked histamine release

The effects of three K⁺-channel blockers, quinine, quinidine and sparteine on K⁺-evoked histamine (HA) release have been investigated. KCl (150 mM) initiated 40–55% release of HA from rat peritoneal mast cells in the absence of extracellular Ca⁺⁺, and this could be suppressed by pretreating the cells with K⁺-channel blockers. In the concentration range of 0.05–2 mM, reductions were dose-dependent and the IC₅₀-s (in mM) obtained were 0.15 and 0.25 for quinine and quinidine and 0.20 for sparteine. The light microscopic studies showed close parallelism between the KCl-evoked HA-release and mast cell degranulation in the absence and also in the presence of K⁺-channel blockers. Present results strenghthened the involvement of K⁺-channels in the KCl-evoked HA release and showed that these channels are sensitive to quinine/quinidine and also to sparteine. These data appeared, however, insufficient to clarify fully the mechanism of K⁺-induced HA secretion or to classify the K⁺-channels involved in this mechanism.     

Forskolin inhibits the release of histamine from human basophils and mast cells

We found that forskolin (10^–7 to 3×10^–5 M) caused dose-related inhibition of antigen-induced histamine release from human basophil leukocytes. The dose-response inhibition curve was paralleled by a forskolin-induced increase in cyclic AMP (cAMP) levels in human leukocyte preparations. The kinetics of inhibition of histamine release and of the increase in leukocyte cAMP were the same.In a second series of experiments we evaluated the effect of forskolin on antigen-induced histamine release from chopped human lung passively sensitized with serum from an allergic patient. Forskolin (10^–7 to 3×10^–5 M) dosedependently inhibited the release of histamine from human lung mast cells. Thus forskolin appears to modulate the release of mediators of the immediate hypersensitivity reaction, presumably through activation of adenylate cyclase in human basophils and mast cells.Supported by Grants from the C.N.R. (83.00430.04 and 84.01756.04) and M.P.I. (Rome, Italy).     

Ion channels regulating mast cell biology

Mast cells play a central role in the pathophysiology of asthma and related allergic conditions. Mast cell activation leads to the degranulation of preformed mediators such as histamine and the secretion of newly synthesised proinflammatory mediators such as leukotrienes and cytokines. Excess release of these mediators contributes to allergic disease states. An influx of extracellular Ca²⁺ is essential for mast cell mediator release. From the Ca²⁺ channels that mediate this influx, to the K⁺, Cl^? and transient receptor potential channels that set the cell membrane potential and regulate Ca²⁺ influx, ion channels play a critical role in mast cell biology. In this review we provide an overview of our current knowledge of ion channel expression and function in mast cells with an emphasis on how channels interact to regulate Ca²⁺ signalling.     

Differential modulation of mediator release from human basophils and mast cells by mizolastine

BACKGROUND: Basophils and mast cells play a major role in the pathogenesis of allergic disorders by releasing several proinflammatory mediators. Some histamine H1 receptor antagonists exert anti-inflammatory activities by modulating mediator release from basophils and mast cells. OBJECTIVE: To study the in vitro effects of mizolastine, an H1 receptor antagonist, on the release of eicosanoids, histamine and IL-4 from human basophils and lung mast cells. METHODS AND RESULTS: Mizolastine (10(-7)-10(-5) M) concentration-dependently inhibited the release of cysteinyl leukotriene C4 from anti-IgE-stimulated basophils (IC(50): 3.85+/-0.28 microM) and mast cells (IC(50): 3.92+/-0.41 microM). The same concentrations of mizolastine did not affect anti-IgE-induced prostaglandin D2 release from lung mast cells. In contrast, mizolastine enhanced up to 80% IgE-mediated histamine release (EC(50): 4.63+/-0.14 microM) from basophils, but not from mast cells and it significantly potentiated IL-4 release from basophils induced by anti-IgE. Mizolastine did not affect histamine release from basophils induced by formyl peptide, whereas it inhibited cysteinyl leukotriene C4 release (IC(50): 1.86+/-0.24 microM). Blockade of cytosolic phospholipase A2 and arachidonic acid mobilization by pyrrolidine-1 did not alter the effect of mizolastine on histamine release from basophils, thereby excluding accumulation of arachidonic acid metabolic intermediates as the cause of this effect. Mizolastine did not influence anti-IgE-induced activation of extracellular signal-regulated kinase-1 and -2 (ERK-1 and -2) in human basophils. CONCLUSIONS: Mizolastine efficiently inhibits LTC4 synthesis in human basophils and mast cells presumably by interfering with 5-lipoxygenase. In contrast, it enhances histamine and IL-4 release only from anti-IgE-stimulated basophils. Therefore, mizolastine differentially regulates the production of mediators from basophils and mast cells in a cell- and stimulus-specific fashion.     

Chemokines and Chemokine Receptors: Their Role in Allergic Airway Disease

One of the hallmarks of allergic pulmonary disorders is the accumulation of an abnormally large number of leukocytes including eosinophils, neutrophils, lymphocytes, basophils, and macrophages in the lung (1). There is now substantial evidence that eosinophils, under the control of T lymphocytes, are major effector cells in the pathogenesis of asthma. Therefore, understanding the mechanisms by which eosinophils accumulate and are activated in tissues is a fundamental question very relevant to allergic diseases. Another characteristic of allergic inflammation is the activation of leukocytes resulting in the release of biologically active mediators, such as histamine from mast cells and basophils. It is now apparent that chemokines are potent leukocyte chemoattractants, cellular activating factors, histamine releasing factors, and regulators of homeostatic immunity, making them particularly important in the pathogenesis of airway inflammation in asthma (2). In this regard, chemokines are attractive new therapeutic targets for the treatment of allergic disease. This article focuses on recently emerging data on the importance of chemokines and their receptors in allergic airway inflammation.     

Basophils in skin inflammation

Basophils represent less than 1% of peripheral blood leukocytes. Under physiological conditions, basophils principally circulate in peripheral blood, while mast cells reside in peripheral tissues. Like mast cells, they express the high-affinity IgE receptor on their cell surface and release chemical mediators. Because of morphological and functional similarities, basophils have long been considered to be redundant "circulating mast cells" and minor (probably negligible) players in inflammation. Mouse and human basophils cannot be stained in routinely processed histological specimens, and thus, our understanding of tissue basophils in allergic inflammation had been limited. However, recent studies in mice have revealed that basopihls play non-redundant roles from mast cells. Basophils function as a source of IL-4, IL-13, and CCL22, thereby contributing Th2 immunity. They are also capable of presenting antigens. Basophils are essential for the development of IgE-mediated chronic allergic skin inflammation in mice. Recent immunohistochemical studies with an basophil-specific antibody revealed that, in humans, varying numbers of basophils infiltrate skin lesions of inflammatory diseases, such as atopic dermatitis, urticaria, prurigo, and eosinophilic pustular folliculitis. Basophils may play important roles in a variety of inflammatory skin diseases than previously thought.     

Chemical constituents of diesel exhaust particles induce IL-4 production and histamine release by human basophils

BACKGROUND: An epidemiologic relationship between airway allergic diseases and exposure to atmospheric pollutants has been demonstrated and suggested to be one factor in the increasing prevalence of asthma. Diesel exhaust particles (DEPs) have been shown to participate in the development of allergic airway inflammation, in which the targets include macrophages, B and T cells, epithelial cells, and mast cells. In addition to the adjuvant effect of DEPs on total and allergen-specific IgE production, DEPs also act to induce chemokines and cytokines and may play a key role in primary sensitization. OBJECTIVE: DEPs have been shown to increase local IL-4-containing Kit(+) cells soon after in vivo nasal challenge. The aim of this study was to examine the effects of DEPs on human basophils, a key source of IL-4. METHODS: Peripheral blood leukocytes from allergic and control subjects were cultured in the presence of organic extracts of DEP (DEPex) with or without allergen. The cultures were analyzed for IL-4-containing cells by using multiparameter flow cytometry, IL-4 secretion with ELISA, and histamine release. RESULTS: Basophils, when exposed in vitro to DEPex, expressed IL-4 and released histamine significantly (P <.01) more than with antigen activation. DEPex did not synergize with allergen in cytokine production and histamine release. DEPex-induced basophil IL-4 expression peaked at 2 hours and persisted through 20 hours, in contrast to allergen-induced IL-4, which was transient. The effect of DEPex on basophil cytokine expression and histamine release was dose dependent and occurred with cells from both allergic and nonallergic subjects. DEPex induced IL-4 expression and histamine release in highly enriched basophil populations, suggesting it acts directly on basophils. Other peripheral blood leukocytes, including T cells, did not contribute to this cytokine expression. Preincubation with N-acetylcysteine completely abrogated DEPex-driven basophil IL-4 expression. CONCLUSIONS: Basophils are a direct target for DEPex, inducing IL-4 expression and histamine release in an IgE-allergen independent fashion. N-acetylcysteine inhibition of DEPex-driven IL-4 expression provides evidence that generation of reactive oxygen species is required for the effects observed. The capability of DEPex to activate basophils in both allergic and nonallergic subjects suggests a potential role of this pollutant in the increasing prevalence of allergic diseases.     

Release of granule proteins from human eosinophils stimulated with mast-cell mediators

Background It has been suggested that mast cells and eosinophils are major effector cells in the pathogenesis of allergic diseases. However, the interaction of these cells has not been thoroughly elucidated. We examined eosinophil cationic protein (ECP) release and cytosolic free calcium concentration ([Ca²⁺]) in human eosinophils induced by the major mast-cell mediators including cytokines. Methods Eosinophils from healthy donors were stimulated with the major mast-cell mediators for 20 min after preincubation with cytochalasin B for 10 min. ECP in supernatants was measured by radioimmunoassay. Moreover, t o examine changes of [Ca²⁺]i in eosinophils, Fura-2-loaded eosinophils were monitored for fluorescence changes after stimulus addition. Results Of the tested mediators (prostaglandin [PG]D₂, leukotriene (LT)B₄, platelet-activating factor (PAF), histamine, LTQ, and eosinophil chemotactic factor of anaphylaxis [ECF-A]), LTB₄ and PAF induced ECP release from eosinophils. Any cytokines produced by human mast cells, i.e., interleukin (IL)-4, IL-5, IL-8, tumor necrosis factor (TNF), or granulocyte-macrophage colony-stimulating factor (GM-CSF), did not induce ECP release in our system. ECP release triggered with LTB₄ and PAF occurred at concentrations of 10^?8-10^?6 M concentration-dependently. LTB4 and PAF also elicited a rise in [Ca²⁺]_i in eosinophils. Neither PGDj, histamine, nor LTC₄ induced ECP release, although they increased cytosolic calcium in eosinophils. Conclusions Of mast-cell mediators, LTB₄ and PAF induced eosinophil degranulation. The contribution of LTB4 and PAF from mast cells to eosinophil degranulation may be important in the pathogenesis of allergic inflammatory diseases.     

Inhibition of potassium-induced release of histamine from mast cells by tetraethylammonium and tetramethylammonium

In accordance with our previous results, a marked release of histamine (HA) from rat peritoneal mast cells was initiated by 150 mM KCl in the absence of extracellular Ca²⁺. This release could be reduced by 20–60 mM tetraethylammonium (TEA) or tetramethylammonium (TMA), the non-selective K⁺-channel blockers, Ouabain, the general inhibitor of (Na⁺+K⁺) ATP-ase, failed to produce any changes in this release. The action of TEA discriminated between the initiation of HA release evoked by different agents, producing a blockade of the K⁺-induced but not the 48/80-stimulated HA release. In total, these data suggest the presence of TEA/TMA-sensitive K⁺-channels in the mast cell membrane and their involvement in one of the possible pathways for the initiation of HA release.     

Modulation of the release of histamine and arachidonic acid metabolites from human basophils and mast cells by auranofin

In these experiments the effects of pharmacological concentrations of auranofin, a new absorbable gold compound, were assessed on the release of histamine and peptide leukotriene C₄ (LTC₄) from human basophils and lung mast cells. Auranofin, at pharmacological concentrations, inhibitedin vitro histamine and LTC₄ release from human basophils induced by anti-IgE. Inhibition began at about 3×10^–7 M and was maximum at 10^–5 M. We also evaluated the effect of auranofin on the release of histamine and LTC₄ induced by anti-IgE from mast cells purified from human lung. Auranofin (3×10^–7 to 10^–5 M) dose-dependently inhibited the release of histamine and LTC₄ from human lung mast cells. Thus pharmacological concentrations of auranofin cause dose-related inhibition of histamine release andde novo synthesis of LTC₄ by human basophils and lung mast cells.Supported in part by grants from the C.N.R. (83.00430.04, 84.01756.04) and (85.00491.04) and M.P.I. (Rome, Italy).     

Effect of Divalent Cations on the Interaction of Adenosine 5‘-Triphosphate (ATP) with Histamine Release Induced by Compound 48/80

The inhibition exerted by ATP on histamine release caused by compound 48/80 from isolated rat mast cells was counteracted by Ca⁺⁺, Mg⁺⁺, Ba⁺⁺, and Sr⁺⁺, but not by Be⁺⁺. In addition, after the inhibitory effect had been obtained by pretreatment of mast cells with ATP, addition of Mg⁺⁺ restored the sensitivity of the cells towards 48/80. The spontaneous restoration of the sensitivity of the mast cells towards 48/80 observed after prolonged pretreatment of the cells with ATP (< 10 μM.) was enhanced by the presence of glucose. Glucose did not effect the inhibition per se. EDTA blocked 1) the protecting effect of divalent cations on the action of ATP on mast cells in regard to their sensitivity towards 48/80, 2) the action of Mg⁺⁺ to restore the sensitivity of mast cells towards 48/80 after rendered insensitive by treatment with ATP, 3) the spontaneous restoration of the sensitivity of ATP-treated mast cells towards 48/80 observed after prolonged incubation alone, as well as the enhanced restoration observed in the presence of glucose. The results suggest an interaction between divalent cations and ATP on the plasma membrane.     

The role of calcium in the repetitive firing of neostriatal neurons

Summary The Ca⁺⁺-dependence of the repetitive firing of neostriatal neurons was studied in an in vitro slice preparation of the rat neostriatum. Neuronal firing was evoked by injecting depolarizing currents of 100–200 ms duration. In normal conditions, the mode of firing was tonic and showed very little adaptation. The frequency-current relation was linear over a wide range of frequencies. The repetitive firing was first enhanced and later suppressed by Co⁺⁺, Mn⁺⁺ and Cd⁺⁺. These effects on the repetitive firing by the Ca⁺⁺-channel blockers paralleled the suppression of the slow afterhyperpolarizing potential. The lowering (0.2 mM) of Ca⁺⁺ had similar effects. In the presence of TEA (up to 10 mM), the cell fired both Na⁺ and Ca⁺ action potentials. The results suggest that, as in other CNS neurons of the vertebrate, in neostriatal neurons the slow afterhyperpolarizing potential (AHP) is due to a Ca⁺⁺-activated K⁺-conductance, and that the AHP plays a crucial role in the repetitive firing of these neurons.     

Mucosal T-cell phenotypes in persistent atopic and nonatopic rhinitis show an association with mast cells

Background: Allergic rhinitis is characterized by selective expansion of T cell subsets with a CD4+ phenotype. Recently, we identified a subpopulation of nonallergic rhinitis subjects with increased epithelial mast cell and eosinophil populations, suggestive of local mucosal allergy. Previously, T cell subsets have not been characterized in this subselection of nonallergic subjects and furthermore, their relationship to mast cell and basophil effector cells remain unidentified. Objective: To determine if a subpopulation of nonallergic subjects with idiopathic rhinitis (IR) have localized allergy confined to their nasal mucosa by comparing the T cell subsets and major histocompatibility complex (MHC) II expressing cells to persistent allergic rhinitis (PAR). Furthermore, the relationship between T cell subsets and mast cells/basophils was investigated. Methods: None of the symptomatic patients in this study were clinically allergen‐challenged. Nasal turbinate mucosa was removed from patients with PAR, IR and normal controls. Morphometry was performed on immunostained sections for T cell subset populations including CD3+, CD4+, CD8+, CD25+, CD45RA+, CD45RO+, human leucocyte antigen (HLA)‐DRα (MHC class II), mast cell tryptase and for basophils. Results: Subjects with persistent allergic rhinitis differed to normal controls in showing significantly increased numbers of total (CD3+), activated (CD25+) and allergen‐naïve (CD45RA+) T lymphocytes in their nasal mucosa (P < 0.025). The naïve CD45RA+ memory T cells correlated to mucosal mast cells in PAR (P = 0.03). IR patients differ to allergic subjects in showing significantly reduced numbers of epithelial HLA‐DRα+ cells (P = 0.007), but increased numbers of CD8+ lymphocytes (P = 0.02). The CD8+ T cells correlated with mucosal mast cell numbers (P = 0.02). In both rhinitis groups, basophils were present in very low numbers obviating the need for statistical analysis. Conclusion: PAR is characterized by increased numbers of CD3+, CD25+ and CD45RA+ T lymphocytes compared with normal mucosa. Allergic and nonallergic rhinitis groups can be separated by significant differences in the number of epithelial antigen presenting cells (APCs) (HLA‐DRα+) and sub‐epithelial activated (CD25+) T cells. Moreover, IR patients do not significantly differ to their allergic counterparts with respect to total (CD3+) and naïve (CD45RA+) T cell numbers, or numbers of epithelial activated (CD25+) lymphocytes. IR subjects show significantly increased numbers of CD8+ lymphocytes compared with control mucosa and although our findings suggest that the initiating inflammatory events may differ, both rhinitis groups show a similarity in pathology involving mucosal mast cells with an association to infiltrating T cells.     

Adenosine triphosphatase in non-secreting and secreting mast cells

A Ca⁺⁺–Mg⁺⁺ ATPase has been demonstrated in the plasma membrane of rat peritoneal mast cells. The enzyme is localized by electron microscopy on the outer surface of the membrane. This agrees with the biochemical findings. A Ca⁺⁺–Mg⁺⁺ activated ATPase has also been shown to be present in the granule membrane. The optimal pH of the plasma membrane enzyme is close to the optimal pH for histamine release. All the 14 inhibitors of plasma membrane ATPase tested-which caused varying degrees of inhibition of the enzyme-also inhibited histamine release induced by antigen, compound 48/80 and the divalent ionophore A23187. The conclusion from the study with the inhibitors is that a mild inhibition of the enzyme is compatible with histamine release, but a pronounced inhibition of the enzyme is always associated with inhibition of histamine release. ATP in low concentrations potentiates the release.     

Antigen-induced histamine release from mast cells and basophils after hydrocortisone and disodium cromoglycate treatment

The effect of drugs applied in the treatment of allergic diseases such as hydrocortisone and disodium cromoglycate-Intal^® on the release of histamine during immediate allergic response was investigated. Experiments carried out on guinea-pigs showed that after hydrocortisone administration the blood histamine level fell, whereas the histamine concentration in the lung tissue varied, depending on the time of the drug administration in relation to the antigen challenge. Disodium cromoglycate given before induction of an asthma attack in guinea-pigs lowered the histamine level in the blood and in the lung tissue homogenates. Investigations were also carried out on isolated rat mast cells and human basophils. The stabilizing effect of hydrocortisone was much weaker than that of dosodium cromoglycate especially regarding mastocytes. It was found that the extent of histamine release from mastocytes and basophils depends on the concentration of the drugs applied and on the type of antigen used for induction of cell degranulation.     

Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human FcɛRI+cells

Background Loratadine, a novel histamine H₁-receptor antagonist, is effective in the treatment of patients with seasonal and perennial rhinitis and some allergic skin disorders. Histamine and other chemical mediators are synthesized and immunologically released by human peripheral blood basophils and tissue mast cells (Fc?RI⁺ cells). Objective To evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl-loratadine (des-loratadine), on the immunological release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C₄: LTC₄ and prostaglandin D₂: PGD₂) from human Fc?RI⁺ cells. Methods Human Fc?RI⁺ cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated with loratadine and des-loratadine before immunological challenge with Der p 1 antigen or anti-Fc?RI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human FcRI⁺ cells. Results Preincubation (15m in, 37°C) of purified (36–74%) basophils with loratadine (3 × 10^–6–10^–4M) and des-loratadine before Der p 1 antigen or anti-Fc?RI challenge concentration-dependency (5–40%) inhibited the release of histamine and LTC₄. Loratadine (3 × 10^–6–l0^–4M) and des-loratadine also inhibited (10–40%) histamine, LTC₄, and PGD₂ release from purified HLMC (16–68%) activated by anti-Fc?RI. Loratadine (3 × 10^–6–10^–4M) and des-loratadine caused concentration-dependent inhibition (10–40%) of histamine, tryptase. LTC₄, and PGD₂ release from purified HSMC (24– 72%) immunologically challenged with anti-Fc?RI. Conclusion These results indicate that loratadine and its main metabolite have anti- inflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human Fc?RI⁺ cells.     

Inhibition of histamine release and ionophore-induced calcium flux in rat mast cells by lidocaine and chlorpromazine

We studied the effects of lidocaine (L) and chlorpromazine (C), two compounds known to affect the binding of calcium to cell membranes, on histamine release and⁴⁵calcium uptake by purified mast cells upon challenge with the ionophore A23,187 or with compound 48/80. At low concentrations L and C inhibited the Ca⁺⁺ flux as well as histamine release while higher concentrations caused enhancement in this function. Evidence was obtained that L 10^–4 M may displace Ca⁺⁺ from the cell membranes.Presented in part at the Annual Meeting of The American Academy of Allergy, San Juan, P.R., March 5, 1976.     

Basophils from patients with allergic asthma show a primed phenotype.

BACKGROUND: IL-3, IL-5, and GM-CSF are not able to induce histamine release in purified basophils of nonallergic donors. However, we have recently found that preincubation with 2 micromol/L thapsigargin, which induces a rise in intracellular free calcium ions, renders human basophils extremely sensitive for IL-3, IL-5, or GM-CSF, leading to enhanced histamine release. Histamine release was also induced in the reverse order (first cytokine and then thapsigargin). OBJECTIVE: Because these cytokines are supposed to be increased in allergic inflammation, we examined whether basophils of patients with allergic asthma showed an enhanced response to thapsigargin. METHODS: We measured the histamine release induced by thapsigargin in a group of allergic asthmatic subjects (n = 24) and compared this response with those of 3 control groups. The control groups consisted of healthy control subjects (group 1, n = 21); patients with a nonallergic, nonasthmatic lung disease (group 2, n = 22); and patients with nonallergic asthma (group 3, n = 9). RESULTS: There was no difference in spontaneous histamine release. Also, no significant difference in histamine release was found when anti-IgE or formyl-methionyl-leucyl-phenylalanine was used as a stimulus. Histamine release induced by IL-3 alone or a combination of IL-3 and thapsigargin also did not differ. In contrast, basophils from the group with allergic asthma showed a significantly higher percentage of histamine release induced by thapsigargin (38.2% +/- 13.2%) than did basophils from the 3 control groups (healthy control subjects, 22.5% +/- 6.9%; subjects with lung disease, 24.9% +/- 8.9%; subjects with nonallergic asthma 15.0% +/- 3.0%; all mean +/- SD). CONCLUSION: These data indicate that basophils in peripheral blood of subjects with allergic asthma have a primed phenotype and that thapsigargin-induced histamine release is a practical tool to study this phenomenon.